Infectious diseases caused by the various bacteria remain one of most dangerous threats to human beings despite the availability of several antibiotics and vaccines. The misuse or overuse of antibacterial agents led to the emergence of multidrug resistant bacterial pathogens. In addition, bacteria often resilient enough to survive in even the extreme environments through evolution of different mechanisms. Hence, there is an urgent need for novel antibacterials to address resistance with novel mechanisms. Hunanamycin A is the first natural product with a pyrido[1,2,3-de]quinoxaline-2,3-dione core related to a degradation product of riboflavin (vitamin-B2).
Article titled “One-pot efficient green synthesis of 1,4-dihydro-quinoxaline-2,3-dione derivatives “by J. Chem. Sci., 2006, 118 (5), pp. 425-428 reports newer and cleaner processes for organic transformations and Synthesis of these potential pharmacophore 1,4-dihydro-quinoxaline-2,3-dione. They report simple solid phase grinding of substituted o-phenylinediamine and oxalic acid at room temperature in good yield.
Article titled “Mitsunobu and Related Reactions: Advances and Applications” by K. Swamy et al. published in Chem. Rev., 2009, 109 (6), pp 2551-2651 reports the reaction involves C—O, C—S, C—N, or C—C bond formation by the condensation of an acidic component with a primary or a secondary alcohol in the presence of triphenylphosphine (or another suitable phosphine) and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD).
Article titled, “Hunanamycin A, an Antibiotic from a Marine-Derived Bacillus hunanensis' by MacMillan et al. published in Org. Lett., 2013, 15 (2), pp 390-393 isolation of hunanamycin A from a marine-derived bacteria Bacillus hunanensis by. Also reports Hunanamycin A exhibits a minimum inhibitory concentration (MIC) of 12.4 μM against the bacterial pathogen Salmonella enterica. The gross structure and stereo chemical assignments of hunanamycin A were predicted using extensive spectroscopic data analysis and by comparing the data with riboflavin, a structurally relevant compound. As the structure of hunanamycin A was related to riboflavin degradation products, MacMillan group screened it for antimicrobial activity against bacterial strains that lacked riboflavin transport mechanisms. The compound hunanamycin A showed minimum inhibitory concentration (MIC) of 12.4 μM against Salmonella enterica suggesting it is an inhibitor of riboflavin synthase (ribB).
Riboflavin synthase is an enzyme that catalyzes the final step in the biosynthesis of riboflavin. In disease models of Salmonella infection, knockout of the riboflavin synthase was shown to be lethal to the pathogen. The target ribB has been shown to be an attractive antibiotic target as human beings lack this target. As the target compound hunanamycin A showed to be selective towards the inhibition of Salmonella enterica (based on screening with limited no. of organisms), the scaffold may be used for the development of antibacterial agents for killing Salmonella bacteria.
